Letter to the Editor: Mucosal gut microbiota in primary sclerosing cholangitis before and after liver transplantation—Are there other challenges?
Authors: Burcin Ekser, Serkan Sucu, Plamen Mihaylov, Juliet A. Emamaullee
Journal: Hepatology (2023)

To the editor, We read with great interest the article by Hole et al,1 which studied the mucosal gut microbiota in primary sclerosing cholangitis (PSC) before and after liver transplantation (LT). Although the authors concluded that mucosa-associated dysbiosis did not improve after LT in PSC patients, which correlated with disease severity and survival, they claimed that a specific mucosal gut microbiota predicted PSC recurrence following LT. In the same issue, an editorial by Hartmann and Schnabl2 also highlighted the importance of the study on the identification of a specific mucosa-adherent microbial signature in PSC severity and recurrence following LTs. The study is one of the largest cohorts which studied the gut microbiota after LT. However, we have certain doubts whether all variables were appropriately included; Did they use a piggyback or bicaval technique? Were the bile duct anastomoses performed using duct-to-duct or Roux-en-Y choledocojejunostomy fashion? What were the model for end-stage liver disease scores? What time points were mucosal samples collected before and after LTs? (eg, 1 month or 1 y before and after LT) If pre-LT samples were collected immediately before LT, was there any spontaneous bacterial peritonitis? Since the recurrence rate of PSC was relatively high (25%), did the authors observe good trough levels of tacrolimus throughout the follow-up? Did they use any induction treatment (eg, anti-thymocyte globulin)? What was the rejection rate? How were they treated? How did the rejection impact the survival and tissue sampling time? The abovementioned variables could potentially change the outcome since variables in Table 1 were demonstrated to affect the gut microbiota previously.3 Moreover, the study by Hole et al1 would be able to answer certain questions changing our understanding of PSC patients' gut microbiota following LT with further analysis, such as a comparison of (A) piggyback LT with prolonged portal vein clamping and intestinal edema/stasis versus bicaval LT, (B) duct-to-duct bile duct anastomosis versus Roux-en-Y choledecojejunostomy, which the latter is commonly performed in PSC and changes the intestinal integrity and directions, and (C) rejection versus rejection-free patients following LT. TABLE 1 - Variables demonstrated to affect the gut microbiota in liver transplantation Antibiotic and probiotic use before and after transplantation Immunosuppression (and low and high trough levels) Timing of sample collection before and after transplantation Rejection of the allograft We believe that Hole et al1 could potentially answer many unknowns regarding the impact of LT on gut microbiota following PSC if the abovementioned clinical variables4 will be further taken into consideration. It was also previously shown that intestinal dysbiosis was independent of inflammatory bowel disease in PSC patients,5 therefore further subgrouping for PSC versus PSC-inflammatory bowel disease would not be necessary.